Assessment of Atrial Tissue Obtained From Patients Undergoing Heart Surgery and Tissue Banking

Over the past decade, techniques have been refined which permit an enormous amount of information relevant to disease mechanisms to be gained from the examination of heart tissue. The Cardiovascular Institute has extensive experience with these techniques, and has utilized them to examine other heart disease substrates. In this study, the investigators propose to obtain heart tissue at the time of cardiac surgery which would otherwise be discarded. Their plan is to examine this tissue and correlate their findings with clinical data. Their hope is that the proposed study will provide insight into atrial physiology, including the molecular mechanisms underlying atrial disease and the potential development of atrial fibrillation (AF).

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Other: atrial tissue

Detailed Description

Atrial fibrillation (AF), a disorder of heart rhythm, is epidemic in the United States, affecting nearly 3 million people. AF arises in a variety of settings, often in association with other cardiac disease. Demographic and clinical factors can be utilized to profile "at-risk" patients, but the predictive value of such algorithms is low. The reasons for this presumably relate to the fact that these factors are interacting with the tissue substrate in a variable way. In addition, correlations such as these provide no insight into mechanisms associated with the development of AF in patients without other known heart disease, which is commonplace. Over the past decade, techniques have been refined which permit an enormous amount of information relevant to disease mechanisms to be gained from examination of heart tissue. The Cardiovascular Institute has extensive experience with these techniques, and has utilized them to examine other heart disease substrates. In this study, we propose to obtain heart tissue at the time of cardiac surgery which would otherwise be discarded.

Our plan is to examine this tissue and correlate our findings with clinical data. Our hope is that the proposed study will provide insight into atrial physiology, including the molecular mechanisms underlying atrial disease and the potential development of AF.

This will be a prospective tissue bank for atrial tissue. We propose an enrollment of 300 subjects, to take place at UPMC Presbyterian over a 5 year period. Subjects will be recruited from among those patients referred for non-emergent surgery on the heart for standard indications. The patient's medical record will be reviewed and health information recorded that includes but is not limited to demographics, heart disease history, other past medical history, lab work,drug therapy,and all cardiac testing the patient has undergone prior to surgery. Patients undergoing surgery will have residual atrial tissue which would otherwise be discarded (related to cannulation and/or appendectomy). Thus, obtaining this tissue will have no effect on the flow, duration, or outcome of the operative procedure.

Tissue assessment will include:

• Microscopic histology using standard tissue stains; and
• Characterization of gene expression.

Characterization of gene expression will be performed using a multiplicity of techniques which focus on DNA, RNA and proteins produced by the various cells comprising atrial tissue. Expression of a variety of genes known to be important in other cardiac diseases will be analyzed. In addition, expression of novel genes previously not known to be relevant to heart disease may be examined.

Tissue assessment data will be correlated with clinical data including preoperative AF history, demographic information, features of the medical history, details of cardiac structure/function(obtained by examining preoperative tests performed for standard indications), and the incidence of postoperative AF as a first arrhythmia diagnosis.

• Study Type: Observational
• Enrollment (Actual): 37

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects are patients of UPMC Cardiothoracic Surgery who are having standard of care open heart surgery

Description

Inclusion Criteria:

• 18 years or over
• Referred for heart surgery for standard indication
• Competent to give informed consent

Exclusion Criteria:

• Inability to give informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
nonemergent heart surgery, atrial tissue; patients undergoing non-emergent heart surgery	Other: atrial tissue; retrieval of discarded atrial tissue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evidence of atrial physiology	Normally discarded atrial tissue samples will be collected at the time of cardiac surgery and microscopic histology will be performed using standard tissue stains	Visit 1, Atrial tissue sample obtained at the time of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evidence of underlying molecular mechanisms of atrial disease	Normally discarded atrial tissue samples will be collected at the time of cardiac surgery and the samples will be assayed for gene expression	Visit 1, Atrial tissue samples obtained at the time of surgery

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Investigators: Principal Investigator: Yingze Zhang, PhD, University of Pittsburgh

Publications and helpful links

General Publications

• Li YY, Feldman AM, Sun Y, McTiernan CF. Differential expression of tissue inhibitors of metalloproteinases in the failing human heart. Circulation. 1998 Oct 27;98(17):1728-34. doi: 10.1161/01.cir.98.17.1728.

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2012
• Primary Completion (Actual): February 17, 2016
• Study Completion (Actual): February 17, 2016

Study Registration Dates

• First Submitted: January 17, 2013
• First Submitted That Met QC Criteria: February 14, 2013
• First Posted (Estimate): February 15, 2013

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 20, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: genetics; atrial fibrillation; heart disease; cardiac arrhythmias
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: PRO12050391

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED